Abstract
Epinephrine and norepinephrine are known inhibitors of pancreatic insulin secretion. Previous work has shown that epinephrine blocks the insulin secretion stimulated by both glucose (3 mg/ml) and dibutyryl cyclic adenosine monophosphate. The present study was designed to determine the nature of the sites in catecholamine structure that influence insulin release. These studies were carried out with an in vitro golden hamster pancreas system. The effect of a series of catecholamine precursors and analogs on glucose-mediated insulin secretion was determined. l-Phenylalanine, l-tyrosine and 3,4-dihydroxy-phenylacetic acid had no effect on insulin release. β-Phenylethylamine, tyramine, dopamine, l-phenylephrine, l-epinephrine, 1-3 ,4-dihydroxyphenylalanine, l-α-methyldopa, l-norepinephrine, dl-metanephrine and dl-isoproterenol inhibited insulin secretion. The inhibitory action of the various catecholamines and analogs on insulin secretion showed a linear log dose relationship. Dopamine was set as a reference standard and the inhibitory action of all the others were expressed relative to it by analysis of variance. This type of analysis indicated that the inhibitory activity of these compounds was dependent on the amine group on the aliphatic chain and the hydroxyl groups on the aromatic ring rather than on alpha or beta stimulating properties. The structural determinants responsible for the effects of catecholamines on glucose-mediated insulin secretion are virtually identical to those previously reported for the indole amine series.
Footnotes
- Received April 27, 1970.
- Accepted November 23, 1970.
- © 1971 by The Williams & Wilkins Co.
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|